1. Field of the Invention
This invention relates to a method and apparatus for non-invasive monitoring of blood substances, particularly glucose, using self-sampled tears.
2. Background Art
The measurement of glucose in blood plasma is perhaps the most important physiologic analyte measurement in medicine, as diabetes has immense public health implications. Diabetes is a leading cause of disability and death, affecting approximately seventeen million Americans. The total annual cost of treating diabetes and its complications in the United States is in excess of $150 billion, a large part of the total national expenditure for health care.
The medical management of diabetes by tight glycemic (blood glucose) control can minimize its devastating kidney, ocular, neurological, and vascular complications, as documented in the National Institutes of Health-sponsored Diabetes Control and Complications Trial. However, the trial resulted in a three-fold increase in hypoglycemic incidents. Of great concern to diabetologists in their care of these patients is hypoglycemia awareness because of its serious risk for morbidity and mortality.
Tight glycemic control requires frequent measurement by the patient of his/her blood glucose levels, which typically requires a “finger stick” to obtain a blood sample up to eight times daily. This procedure is painful and inconvenient for even the most compliant patients, such that limited patient compliance with self-testing is a significant problem in the medical management of this disease. Accordingly, the need for a non-invasive approach to diabetes management is universally recognized to achieve the goal of involving patients in a proactive way in their glycemic control, both in monitoring blood glucose and in insulin delivery.
The tremendous need for a reliable, cost-effective method of non-invasive blood glucose measurement for diabetes management has stimulated hundreds of analytic approaches. The invasiveness of these approaches extends from implanted sensors through a range of less, to minimally, to non-invasive methods. Minimally invasive methods include chemical or spectroscopic measurement of interstitial fluid from the skin obtained by reverse iontophoretic, electroosmotic, or thermal microporation sampling. Among the other technologically sophisticated approaches to glucose measurement are spectroscopy (transcutaneous infrared, fluorescence lifetime, pulsed laser photoacoustic, and far infrared), analysis of breath, optical measurements of the aqueous humor of the eye, polarimetry, and radio wave impedance. Some of these methods have worked well in controlled laboratory testing, but in practice other chemical species, tissue optics, variations in temperature, and other factors have confounded the measurement. For all spectroscopic approaches, the major problem is the need for frequent calibration, as infrared absorption bands for various chemicals in blood or interstitial fluid can overlap significantly and are influenced by temperature and hydrogen bonding effects.
The concentration of low molecular weight analytes, like glucose, in blood plasma is correlated with the levels found in lacrimal fluid, or tears. While a number of methods for measuring this analyte have been applied to tears, two main factors have prevented the practical use of measuring tear glucose concentration as a means for self-monitoring blood glucose concentration: 1) the low level of glucose in tears, reported in a recent study (see Chen et al., J Cap Elec 1996; 5:243–248) to be approximately 1/25 the level in blood, and 2) the small volume of tear fluid as compared with blood that is readily available for analysis. In the aforementioned Chen study, glucose concentration in microliter samples of human tears obtained with capillary tubes was determined by capillary electrophoresis (CE) with laser-induced fluorescence (LIF), a sophisticated method limited to research chemistry laboratories because of its technical complexity.
Currently, no practical, entirely non-invasive system and method exists for patients to self-monitor their blood glucose with the level of accuracy and responsiveness required.